Sphingosine-1-phosphate inhibits the adipogenic differentiation of 3T3-L1 preadipocytes

Moon,Myung-Hee; Jeong,Jae-Kyo; Lee,You-Jin; Seol,Jae-Won; Park,Sang-Youel

doi:10.3892/ijmm.2014.1856

Sphingosine-1-phosphate inhibits the adipogenic differentiation of 3T3-L1 preadipocytes

Authors:
- Myung-Hee Moon
- Jae-Kyo Jeong
- You-Jin Lee
- Jae-Won Seol
- Sang-Youel Park
View Affiliations

Affiliations: Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk 561-756, Republic of Korea
Published online on: July 16, 2014 https://doi.org/10.3892/ijmm.2014.1856
Pages: 1153-1158

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Sphingosine-1-phosphate (S1P) is a pluripotent lipid mediator that transmits signals through G-protein-coupled receptors to control diverse biological processes. The novel biological activity of S1P in the adipogenesis of 3T3-L1 preadipocytes was identified in the present study. S1P significantly decreased lipid accumulation in maturing preadipocytes in a dose‑dependent manner. In order to understand the anti‑adipogenic effects of S1P, preadipocytes were treated with S1P, and the change in the expression of several adipogenic transcription factors and enzymes was investigated using quantitative RT-PCR. S1P downregulated the transcriptional levels of the peroxisome proliferator-activated receptor γ, CCAAT/enhancer binding proteins and adiponectin, which are markers of adipogenic differentiation. The effects of S1P on the levels of mitogen‑activated protein kinase (MAPK) signals in preadipocytes were also investigated. The activation of JNK and p38 were downregulated by S1P treatment in human preadipocytes. In conclusion, the results of this study suggest that S1P alters fat mass by directly affecting adipogenesis. This is mediated by the downregulation of adipogenic transcription factors and by inactivation of the JNK and p38 MAPK pathways. Thus, selective targeting of the S1P receptors and sphingosine kinases may have clinical applications for the treatment of obesity.

View Figures

View References

1	Lei F, Zhang XN, Wang W, et al: Evidence of anti-obesity effects of the pomegranate leaf extract in high-fat diet induced obese mice. Int J Obes (Lond). 31:1023–1029. 2007. View Article : Google Scholar : PubMed/NCBI
2	Boyle KB, Hadaschik D, Virtue S, et al: The transcription factors Egr1 and Egr2 have opposing influences on adipocyte differentiation. Cell Death Differ. 16:782–789. 2009. View Article : Google Scholar : PubMed/NCBI
3	Kim KJ, Lee OH and Lee BY: Fucoidan, a sulfated polysaccharide, inhibits adipogenesis through the mitogen-activated protein kinase pathway in 3T3-L1 preadipocytes. Life Sci. 86:791–797. 2010. View Article : Google Scholar
4	Gregoire FM, Smas CM and Sul HS: Understanding adipocyte differentiation. Physiol Rev. 78:783–809. 1998.PubMed/NCBI
5	Yanagiya T, Tanabe A and Hotta K: Gap-junctional communication is required for mitotic clonal expansion during adipogenesis. Obesity (Silver Spring). 15:572–582. 2007. View Article : Google Scholar : PubMed/NCBI
6	Rayalam S, Della-Fera MA and Baile CA: Phytochemicals and regulation of the adipocyte life cycle. J Nutr Biochem. 19:717–726. 2008. View Article : Google Scholar : PubMed/NCBI
7	Lee H, Lee YJ, Choi H, Ko EH and Kim JW: Reactive oxygen species facilitate adipocyte differentiation by accelerating mitotic clonal expansion. J Biol Chem. 284:10601–10609. 2009. View Article : Google Scholar : PubMed/NCBI
8	Wakabayashi K, Okamura M, Tsutsumi S, et al: The peroxisome proliferator-activated receptor gamma/retinoid X receptor alpha heterodimer targets the histone modification enzyme PR-Set7/Setd8 gene and regulates adipogenesis through a positive feedback loop. Mol Cell Biol. 29:3544–3555. 2009. View Article : Google Scholar
9	Tontonoz P and Spiegelman BM: Fat and beyond: the diverse biology of PPARgamma. Annu Rev Biochem. 77:289–312. 2008. View Article : Google Scholar : PubMed/NCBI
10	Rosen ED and MacDougald OA: Adipocyte differentiation from the inside out. Nat Rev Mol Cell Biol. 7:885–896. 2006. View Article : Google Scholar : PubMed/NCBI
11	Nerurkar PV, Lee YK and Nerurkar VR: Momordica charantia (bitter melon) inhibits primary human adipocyte differentiation by modulating adipogenic genes. BMC Complement Altern Med. 10:342010. View Article : Google Scholar
12	Xing Y, Yan F, Liu Y and Zhao Y: Matrine inhibits 3T3-L1 preadipocyte differentiation associated with suppression of ERK1/2 phosphorylation. Biochem Biophys Res Commun. 396:691–695. 2010. View Article : Google Scholar : PubMed/NCBI
13	Bost F, Aouadi M, Caron L and Binétruy B: The role of MAPKs in adipocyte differentiation and obesity. Biochimie. 87:51–56. 2005. View Article : Google Scholar : PubMed/NCBI
14	Alonso-Vale MI, Peres SB, Vernochet C, Farmer SR and Lima FB: Adipocyte differentiation is inhibited by melatonin through the regulation of C/EBPbeta transcriptional activity. J Pineal Res. 47:221–227. 2009. View Article : Google Scholar
15	Chen TH, Chen WM, Hsu KH, Kuo CD and Hung SC: Sodium butyrate activates ERK to regulate differentiation of mesenchymal stem cells. Biochem Biophys Res Commun. 355:913–918. 2007. View Article : Google Scholar : PubMed/NCBI
16	Johnstone ED, Chan G, Sibley CP, Davidge ST, Lowen B and Guilbert LJ: Sphingosine-1-phosphate inhibition of placental trophoblast differentiation through a G(i)-coupled receptor response. J Lipid Res. 46:1833–1839. 2005. View Article : Google Scholar : PubMed/NCBI
17	Goetzl EJ, Wang W, McGiffert C, Liao JJ and Huang MC: Sphingosine 1-phosphate as an intracellular messenger and extracellular mediator in immunity. Acta Paediatr Suppl. 96:49–52. 2007. View Article : Google Scholar : PubMed/NCBI
18	He X, H’ng SC, Leong DT, Hutmacher DW and Melendez AJ: Sphingosine-1-phosphate mediates proliferation maintaining the multipotency of human adult bone marrow and adipose tissue-derived stem cells. J Mol Cell Biol. 2:199–208. 2010. View Article : Google Scholar
19	Schüppel M, Kürschner U, Kleuser U, Schäfer-Korting M and Kleuser B: Sphingosine 1-phosphate restrains insulin-mediated keratinocyte proliferation via inhibition of Akt through the S1P2 receptor subtype. J Invest Dermatol. 128:1747–1756. 2008.PubMed/NCBI
20	Bieberich E: There is more to a lipid than just being a fat: sphingolipid-guided differentiation of oligodendroglial lineage from embryonic stem cells. Neurochem Res. 36:1601–1611. 2011. View Article : Google Scholar : PubMed/NCBI
21	Pyne S and Pyne NJ: Sphingosine 1-phosphate signalling in mammalian cells. Biochem J. 349:385–402. 2000. View Article : Google Scholar : PubMed/NCBI
22	Ryu J, Kim HJ, Chang EJ, Huang H, Banno Y and Kim HH: Sphingosine 1-phosphate as a regulator of osteoclast differentiation and osteoclast-osteoblast coupling. EMBO J. 25:5840–5851. 2006. View Article : Google Scholar : PubMed/NCBI
23	Martino A, Volpe E, Auricchio G, et al: Sphingosine 1-phosphate interferes on the differentiation of human monocytes into competent dendritic cells. Scand J Immunol. 65:84–91. 2007. View Article : Google Scholar : PubMed/NCBI
24	Donati C, Meacci E, Nuti F, Becciolini L, Farnararo M and Bruni P: Sphingosine 1-phosphate regulates myogenic differentiation: a major role for S1P2 receptor. FASEB J. 19:449–451. 2005.PubMed/NCBI
25	Pchejetski D, Nunes J, Sauer L, et al: Circulating sphingosine-1- phosphate inversely correlates with chemotherapy-induced weight gain during early breast cancer. Breast Cancer Res Treat. 124:543–549. 2010. View Article : Google Scholar : PubMed/NCBI
26	Bonhoure E, Pchejetski D, Aouali N, et al: Overcoming MDR-associated chemoresistance in HL-60 acute myeloid leukemia cells by targeting sphingosine kinase-1. Leukemia. 20:95–102. 2006. View Article : Google Scholar : PubMed/NCBI
27	Pchejetski D, Golzio M, Bonhoure E, et al: Sphingosine kinase-1 as a chemotherapy sensor in prostate adenocarcinoma cell and mouse models. Cancer Res. 65:11667–11675. 2005. View Article : Google Scholar : PubMed/NCBI
28	Sauer L, Nunes J, Salunkhe V, et al: Sphingosine kinase 1 inhibition sensitizes hormone-resistant prostate cancer to docetaxel. Int J Cancer. 125:2728–2736. 2009. View Article : Google Scholar : PubMed/NCBI
29	Moon MH, Jeong JK, Seo JS, et al: Bisphosphonate enhances TRAIL sensitivity to human osteosarcoma cells via death receptor 5 upregulation. Exp Mol Med. 43:138–145. 2011. View Article : Google Scholar : PubMed/NCBI
30	Seo JS, Moon MH, Jeong JK, et al: SIRT1, a histone deacetylase, regulates prion protein-induced neuronal cell death. Neurobiol Aging. 33:1110–1120. 2012. View Article : Google Scholar : PubMed/NCBI
31	Tang QQ, Otto TC and Lane MD: Mitotic clonal expansion: a synchronous process required for adipogenesis. Proc Natl Acad Sci USA. 100:44–49. 2003. View Article : Google Scholar : PubMed/NCBI
32	Simon MF, Daviaud D, Pradère JP, et al: Lysophosphatidic acid inhibits adipocyte differentiation via lysophosphatidic acid 1 receptor-dependent down-regulation of peroxisome proliferator-activated receptor gamma2. J Biol Chem. 280:14656–14662. 2005. View Article : Google Scholar : PubMed/NCBI
33	Fu L, Tang T, Miao Y, Zhang S, Qu Z and Dai K: Stimulation of osteogenic differentiation and inhibition of adipogenic differentiation in bone marrow stromal cells by alendronate via ERK and JNK activation. Bone. 43:40–47. 2008. View Article : Google Scholar : PubMed/NCBI
34	Meacci E, Cencetti F, Donati C, et al: Down-regulation of EDG5/S1P2 during myogenic differentiation results in the specific uncoupling of sphingosine 1-phosphate signalling to phospholipase D. Biochim Biophys Acta. 1633:133–142. 2003. View Article : Google Scholar : PubMed/NCBI
35	Liu Y, Wada R, Yamashita T, et al: Edg-1, the G protein-coupled receptor for sphingosine-1-phosphate, is essential for vascular maturation. J Clin Invest. 106:951–961. 2000. View Article : Google Scholar : PubMed/NCBI
36	Chalfant CE and Spiegel S: Sphingosine 1-phosphate and ceramide 1-phosphate: expanding roles in cell signaling. J Cell Sci. 118:4605–4612. 2005. View Article : Google Scholar : PubMed/NCBI
37	Prusty D, Park BH, Davis KE and Farmer SR: Activation of MEK/ERK signaling promotes adipogenesis by enhancing peroxisome proliferator-activated receptor gamma (PPARgamma ) and C/EBPalpha gene expression during the differentiation of 3T3-L1 preadipocytes. J Biol Chem. 277:46226–46232. 2002. View Article : Google Scholar